A Millimeter-scale Single Charged Particle Dosimeter for Cancer Radiotherapy.

This paper presents a millimeter-scale CMOS 64×64 single charged particle radiation detector system for external beam cancer radiotherapy. A 1×1 µm2 diode measures energy deposition by a single charged particle in the depletion region, and the array design provides a large detection area of 512×512 µm2. Instead of sensing the voltage drop caused by radiation, the proposed system measures the pulse width, i.e., the time it takes for the voltage to return to its baseline. This obviates the need for using power-hungry and large analog-to-digital converters. A prototype ASIC is fabricated in TSMC 65 nm LP CMOS process and consumes the average static power of 0.535 mW under 1.2 V analog and digital power supply. The functionality of the whole system is successfully verified in a clinical 67.5 MeV proton beam setting. To our' knowledge, this is the first work to demonstrate single charged particle detection for implantable in-vivo dosimetry.

Lithium inelastic cross-sections and their impact on micro and nano dosimetry of boron neutron capture.

OBJECTIVE: To present a new set of lithium-ion cross-sections for (i) ionization and excitation processes down to 700 eV, and (ii) charge-exchange processes down to 1 keV/u. To evaluate the impact of the use of these cross-sections on micro a nano dosimetric quantities in the context of boron neutron capture (BNC) applications/techniques. Approach: The Classical Trajectory Monte Carlo (CTMC) method was used to calculate Li ion charge-exchange cross sections in the energy range of 1 keV/u to 10 MeV/u. Partial Li ion charge states ionization and excitation cross-sections were calculated using a detailed charge screening factor. The cross-sections were implemented in Geant4-DNA v10.07 and simulations and verified using TOPAS-nBio by calculating stopping power and CSDA range against data from ICRU and SRIM. Further microdosimetric and nanodosimetric calculations were performed to quantify differences against other simulation approaches for low energy Li ions. These calculations were: lineal energy spectra (yf(y) and yd(y)), frequency mean lineal energy (y_F ) ̅, dose mean lineal energy (y_D ) ̅ and ionization cluster size distribution analysis. Microdosimetric calculations were compared against a previous MC study that neglected charge-exchange and excitation processes. Nanodosimetric results were compared against pure ionization scaled cross-sections calculations. Main Results: Calculated stopping power differences between ICRU and Geant4-DNA decreased from 33.78% to 6.9%. The CSDA range difference decreased from 621% to 34% when compared against SRIM calculations. Geant4-DNA/TOPAS calculated dose mean lineal energy differed by 128% from the previous Monte Carlo. Ionization cluster size frequency distributions for Li ions differed by 76% to 344.11% for 21 keV and 2 MeV respectively. With a decrease in the N1 within 9% at 10 keV and agreeing after the 100 keV. With the new set of cross-sections being able to better simulate low energy behaviors of Li ions. Significance: This work shows an increase in detail gained from the use of a more complete set of low energy cross-sections which include charge exchange processes. Significant differences to previous simulation results were found at the microdosimetric and nanodosimetric scales that suggest that Li ions cause less ionizations per path length traveled but with more energy deposits. Microdosimetry results suggest that the BNC's contribution to cellular death may be mainly due to alpha particle production when boron-based drugs are distributed in the cellular membrane and beyond and by Li when it is at the cell cytoplasm regions.

Sensitivity analysis of an asymmetric Monte Carlo beam model of a Siemens Primus accelerator.

The assumption of cylindrical symmetry in radiotherapy accelerator models can pose a challenge for precise Monte Carlo modeling. This assumption makes it difficult to account for measured asymmetries in clinical dose distributions. We have performed a sensitivity study examining the effect of varying symmetric and asymmetric beam and geometric parameters of a Monte Carlo model for a Siemens PRIMUS accelerator. The accelerator and dose output were simulated using modified versions of BEAMnrc and DOSXYZnrc that allow lateral offsets of accelerator components and lateral and angular offsets for the incident electron beam. Dose distributions were studied for 40 × 40 cm² fields. The resulting dose distributions were analyzed for changes in flatness, symmetry, and off-axis ratio (OAR). The electron beam parameters having the greatest effect on the resulting dose distributions were found to be electron energy and angle of incidence, as high as 5% for a 0.25° deflection. Electron spot size and lateral offset of the electron beam were found to have a smaller impact. Variations in photon target thickness were found to have a small effect. Small lateral offsets of the flattening filter caused significant variation to the OAR. In general, the greatest sensitivity to accelerator parameters could be observed for higher energies and off-axis ratios closer to the central axis. Lateral and angular offsets of beam and accelerator components have strong effects on dose distributions, and should be included in any high-accuracy beam model.

Accounting for the fringe magnetic field from the bending magnet in a Monte Carlo accelerator treatment head simulation.

PURPOSE: Monte Carlo (MC) simulation can be used for accurate electron beam treatment planning and modeling. Measurement of large electron fields, with the applicator removed and secondary collimator wide open, has been shown to provide accurate simulation parameters, including asymmetry in the measured dose, for the full range of clinical field sizes and patient positions. Recently, disassembly of the treatment head of a linear accelerator has been used to refine the simulation of the electron beam, setting tightly measured constraints on source and geometry parameters used in simulation. The simulation did not explicitly include the known deflection of the electron beam by a fringe magnetic field from the bending magnet, which extended into the treatment head. Instead, the secondary scattering foil and monitor chamber were unrealistically laterally offset to account for the beam deflection. This work is focused on accounting for this fringe magnetic field in treatment head simulation. METHODS: The magnetic field below the exit window of a Siemens Oncor linear accelerator was measured with a Tesla-meter from 0 to 12 cm from the exit window and 1-3 cm off-axis. Treatment head simulation was performed with the EGSnrc/BEAMnrc code, modified to incorporate the effect of the magnetic field on charged particle transport. Simulations were used to analyze the sensitivity of dose profiles to various sources of asymmetry in the treatment head. This included the lateral spot offset and beam angle at the exit window, the fringe magnetic field and independent lateral offsets of the secondary scattering foil and electron monitor chamber. Simulation parameters were selected within the limits imposed by measurement uncertainties. Calculated dose distributions were then compared with those measured in water. RESULTS: The magnetic field was a maximum at the exit window, increasing from 0.006 T at 6 MeV to 0.020 T at 21 MeV and dropping to approximately 5% of the maximum at the secondary scattering foil. It was up to three times higher in the bending plane, away from the electron gun, and symmetric within measurement uncertainty in the transverse plane. Simulations showed the magnetic field resulted in an offset of the electron beam of 0.80 cm (mean) at the machine isocenter for the exit window only configuration. The fringe field resulted in a 3.5%-7.6% symmetry and 0.25-0.35 cm offset of the clinical beam R(max) profiles. With the magnetic field included in simulations, a single (realistic) position of the secondary scattering foil and monitor chamber was selected. Measured and simulated dose profiles showed agreement to an average of 2.5%/0.16 cm (maximum: 3%/0.2 cm), which is a better match than previously achieved without incorporating the magnetic field in the simulation. The undulations from the 3 stepped layers of the secondary scattering foil, evident in the measured profiles of the higher energy beams, are now aligned with those in the simulated beam. The simulated fringe magnetic field had negligible effect on the central axis depth dose curves and cross-plane dose profiles. CONCLUSIONS: The fringe magnetic field is a significant contributor to the electron beam in-plane asymmetry. With the magnetic field included explicitly in the simulation, realistic monitor chamber and secondary scattering foil positions have been achieved, and the calculated fluence and dose distributions are more accurate.

Comparison of patient megavoltage cone beam CT images acquired with an unflattened beam from a carbon target and a flattened treatment beam.

PURPOSE: To use an imaging beam line (IBL) to obtain the first megavoltage cone-beam computed tomography (MV CBCT) images of patients with a low atomic number (Z) target, and to compare these images to those taken of the same patients with the 6 MV flattened beam from the treatment beam line (TBL). METHODS: The IBL, which produces a 4.2 MV unflattened beam from a carbon target, was installed on a linear accelerator in use for radiotherapy. Provision was made for switching between the IBL and TBL for imaging the same patient with beams from the low-Z and high-Z targets. Dose was quoted as monitor units times the dose per monitor unit for the standard calibration geometry. Images were acquired with institutional approval and patient consent with both the IBL and TBL on a series of 23 patients undergoing radiotherapy. Patients were imaged daily to weekly and aligned to the planning CT using the images. Doses were reduced over the course of treatment to determine the minimum doses required for alignment. Images were assessed offline. RESULTS: IBL MV CBCT images of prostate, head and neck, lung, and abdomen showed improvement in soft tissue contrast for the same dose as the TBL images. Bony anatomy, air cavities, and fiducial markers were sharper. CBCT with a dose of 1 cGy was sufficient for alignment of prostate and head and neck patients based on bony anatomy or implanted gold seeds, 2-4 cGy for lung, abdomen, and pelvis. Photon scatter in the patient had minimal effect on image quality. The metallic hip prosthesis in one patient showed reduced artifacts compared to diagnostic CT. CONCLUSIONS: The IBL has the advantage of improved image quality at the same dose, or reduced dose for the same image quality, over the TBL.

Validation of the final aperture superposition technique to calculate electron output factors and depth dose curves.

The final aperture superposition technique (FAST) is a method to reproduce rapidly the electron-beam depth dose curves and output factors that would be calculated by a full Monte Carlo simulation. FAST uses precalculated Monte Carlo-based differential dose arrays and performs a superposition of open and shielded contributions to account for arbitrarily shaped insert openings. The objective of this work was to refine and validate the accuracy of the FAST method for a full range of treatment parameters. Compared to full simulations, raw FAST calculations tended to underestimate dose near the surface deposited by particles that crossed the shield-opening interface of the insert. In this study, a set of empirical correction curves was derived to reduce the errors from this "collimator effect." FAST and full simulation calculations were compared for every combination of six beam energies (6-21 MeV), four applicator sizes (10-25 cm), and two source-to-surface distances (SSDs) (100 and 110 cm). Validation tests were performed for a total of 192 fields using four sample insert openings: an open insert and 2, 3, and 5 cm diameter circular openings. Calculations were also performed for four patient inserts with irregularly shaped openings. Using the empirical correction curves, systematic errors were reduced, resulting in mean dose differences of less than 1% of the maximum full simulation dose. FAST relative output factors reproduced full simulation output factors to within 3% for all configurations except for the 2 and 3 cm diameter openings for the 6 and 9 MeV beams at 110 cm SSD. The maximum shift between the FAST and full simulation depth dose curves in the 90%-80% fall-off region was less than 3 mm for 97% of the fields. For the patient insert calculations, differences in output factors and mean differences in depth dose curves were within 1.5% with maximum shifts of 1.5 mm in the 90%-80% fall-off region. A small set measurements also demonstrated 3% accuracy in FAST output factors except for a 5% deviation for a 2 cm diameter insert for the 6 MeV beam at 110 cm SSD. These results demonstrate that FAST can be used to provide output factors and depth dose curves for most clinical cases.

Fast, accurate photon beam accelerator modeling using BEAMnrc: a systematic investigation of efficiency enhancing methods and cross-section data.

In this work, an investigation of efficiency enhancing methods and cross-section data in the BEAMnrc Monte Carlo (MC) code system is presented. Additionally, BEAMnrc was compared with VMC++, another special-purpose MC code system that has recently been enhanced for the simulation of the entire treatment head. BEAMnrc and VMC++ were used to simulate a 6 MV photon beam from a Siemens Primus linear accelerator (linac) and phase space (PHSP) files were generated at 100 cm source-to-surface distance for the 10 x 10 and 40 x 40 cm2 field sizes. The BEAMnrc parameters/techniques under investigation were grouped by (i) photon and bremsstrahlung cross sections, (ii) approximate efficiency improving techniques (AEITs), (iii) variance reduction techniques (VRTs), and (iv) a VRT (bremsstrahlung photon splitting) in combination with an AEIT (charged particle range rejection). The BEAMnrc PHSP file obtained without the efficiency enhancing techniques under study or, when not possible, with their default values (e.g., EXACT algorithm for the boundary crossing algorithm) and with the default cross-section data (PEGS4 and Bethe-Heitler) was used as the "base line" for accuracy verification of the PHSP files generated from the different groups described previously. Subsequently, a selection of the PHSP files was used as input for DOSXYZnrc-based water phantom dose calculations, which were verified against measurements. The performance of the different VRTs and AEITs available in BEAMnrc and of VMC++ was specified by the relative efficiency, i.e., by the efficiency of the MC simulation relative to that of the BEAMnrc base-line calculation. The highest relative efficiencies were approximately 935 (approximately 111 min on a single 2.6 GHz processor) and approximately 200 (approximately 45 min on a single processor) for the 10 x 10 field size with 50 million histories and 40 x 40 cm2 field size with 100 million histories, respectively, using the VRT directional bremsstrahlung splitting (DBS) with no electron splitting. When DBS was used with electron splitting and combined with augmented charged particle range rejection, a technique recently introduced in BEAMnrc, relative efficiencies were approximately 420 (approximately 253 min on a single processor) and approximately 175 (approximately 58 min on a single processor) for the 10 x 10 and 40 x 40 cm2 field sizes, respectively. Calculations of the Siemens Primus treatment head with VMC++ produced relative efficiencies of approximately 1400 (approximately 6 min on a single processor) and approximately 60 (approximately 4 min on a single processor) for the 10 x 10 and 40 x 40 cm2 field sizes, respectively. BEAMnrc PHSP calculations with DBS alone or DBS in combination with charged particle range rejection were more efficient than the other efficiency enhancing techniques used. Using VMC++, accurate simulations of the entire linac treatment head were performed within minutes on a single processor. Noteworthy differences (+/- 1%-3%) in the mean energy, planar fluence, and angular and spectral distributions were observed with the NIST bremsstrahlung cross sections compared with those of Bethe-Heitler (BEAMnrc default bremsstrahlung cross section). However, MC calculated dose distributions in water phantoms (using combinations of VRTs/AEITs and cross-section data) agreed within 2% of measurements. Furthermore, MC calculated dose distributions in a simulated water/air/water phantom, using NIST cross sections, were within 2% agreement with the BEAMnrc Bethe-Heitler default case.

Treatment head disassembly to improve the accuracy of large electron field simulation.

PURPOSE: The purposes of this study are to improve the accuracy of source and geometry parameters used in the simulation of large electron fields from a clinical linear accelerator and to evaluate improvement in the accuracy of the calculated dose distributions. METHODS: The monitor chamber and scattering foils of a clinical machine not in clinical service were removed for direct measurement of component geometry. Dose distributions were measured at various stages of reassembly, reducing the number of geometry variables in the simulation. The measured spot position and beam angle were found to vary with the beam energy. A magnetic field from the bending magnet was found between the exit window and the secondary collimators of sufficient strength to deflect electrons 1 cm off the beam axis at 100 cm from the exit window. The exit window was 0.05 cm thicker than manufacturer's specification, with over half of the increased thickness due to water pressure in the channel used to cool the window. Dose distributions were calculated with Monte Carlo simulation of the treatment head and water phantom using EGSnrc, a code benchmarked at radiotherapy energies for electron scatter and bremsstrahlung production, both critical to the simulation. The secondary scattering foil and monitor chamber offset from the collimator rotation axis were allowed to vary with the beam energy in the simulation to accommodate the deflection of the beam by the magnetic field, which was not simulated. RESULTS: The energy varied linearly with bending magnet current to within 1.4% from 6.7 to 19.6 MeV, the bending magnet beginning to saturate at the highest beam energy. The range in secondary foil offset used to account for the magnetic field was 0.09 cm crossplane and 0.15 cm inplane, the range in monitor chamber offset was 0.14 cm crossplane and 0.07 cm inplane. A 1.5%/0.09 cm match or better was obtained to measured depth dose curves. Profiles measured at the depth of maximum dose matched the simulated profiles to 2.6% or better at doses of 80% or more of the dose on the central axis. The profiles along the direction of MLC motion agreed to within 0.16 cm at the edge of the field. There remained a mismatch for the lower beam energies at the edge of the profile that ran parallel to the direction of jaw motion of up to 1.4 cm for the 6 MeV beam, attributed to the MLC support block at the periphery of the field left out of the simulation and to beam deflection by the magnetic field. The possibility of using these results to perform accurate simulation without disassembly is discussed. Phase-space files were made available for benchmarking beam models and other purposes. CONCLUSIONS: The match to measured large field dose distributions from clinical electron beams with Monte Carlo simulation was improved with more accurate source details and geometry details closer to manufacturer's specification than previously achieved.

Image quality & dosimetric property of an investigational imaging beam line MV-CBCT.

To measure and compare the contrast to noise ratio (CNR) as a function of dose for the CBCTs produced by the mega-voltage (MV) imaging beam line (IBL) and the treatment beam line (TBL), and to compare the dose to target and various critical structures of pediatric patients for the IBL CBCT versus standard TBL orthogonal port films. Two Siemens Oncor linear accelerators were modified at our institution such that the MV-CBCT would operate under an investigational IBL rather than the standard 6MV TBL. Prior to the modification, several CBCTs of an electron density phantom were acquired with the TBL at various dose values. After the modification, another set of CBCTs of the electron density phantom were acquired for various doses using the IBL. The Contrast to Noise Ratio (CNR) for each tissue equivalent insert was calculated. In addition, a dosimetric study of pediatric patients was conducted comparing the 1 cGy IBL CBCT and conventional TBL orthogonal pair port films. The CNR for eight tissue equivalent inserts at five different dose settings for each type of CBCT was measured. The CNR of the muscle insert was 0.8 for a 5 cGy TBL CBCT, 1.1 for a 1.5 cGy IBL CBCT and 2.8 for a conventional CT. The CNR of the trabecular bone insert was 2.9 for a 5 cGy TBL CBCT, 5.5 for a 1.5 cGy IBL CBCT and 14.8 for a conventional CT. The IBL CBCT delivered approximately one-fourth the dose to the target and critical structures of the patients as compared to the TBL orthogonal pair port films. The IBL CBCT improves image quality while simultaneously reducing the dose to the patient as compared to the TBL CBCT. A 1 cGy IBL CBCT, which is used for boney anatomy localization, delivers one-fourth the dose as compared to conventional ortho-pair films.

Low dose megavoltage cone beam computed tomography with an unflattened 4 MV beam from a carbon target.

Megavoltage cone beam computed tomography (MVCBCT) is routinely used for visualizing anatomical structures and implanted fiducials for patient positioning in radiotherapy. MVCBCT using a 6 MV treatment beam with high atomic number (Z) target and flattening filter in the beamline, as done conventionally, has lower image quality than can be achieved with a MV beam due to heavy filtration of the low-energy bremsstrahlung. The unflattened beam of a low Z target has an abundance of diagnostic energy photons, detected with modern flat panel detectors with much higher efficiency given the same dose to the patient. This principle guided the development of a new megavoltage imaging beamline (IBL) for a commercial radiotherapy linear accelerator. A carbon target was placed in one of the electron primary scattering foil slots on the target-foil slide. A PROM on a function controller board was programed to put the carbon target in place for MVCBCT. A low accelerating potential of 4.2 MV was used for the IBL to restrict leakage of primary electrons through the target such that dose from x rays dominated the signal in the monitor chamber and the patient surface dose. Results from phantom and cadaver images demonstrated that the IBL had much improved image quality over the treatment beam. For similar imaging dose, the IBL improved the contrast-to-noise ratio by as much as a factor of 3 in soft tissue over that of the treatment beam. The IBL increased the spatial resolution by about a factor of 2, allowing the visualization of finer anatomical details. Images of the cadaver contained useful information with doses as low as 1 cGy. The IBL may be installed on certain models of linear accelerators without mechanical modification and results in significant improvement in the image quality with the same dose, or images of the same quality with less than one-third of the dose.

Benchmarking of Monte Carlo simulation of bremsstrahlung from thick targets at radiotherapy energies.

Several Monte Carlo systems were benchmarked against published measurements of bremsstrahlung yield from thick targets for 10-30 MV beams. The quantity measured was photon fluence at 1 m per unit energy per incident electron (spectra), and total photon fluence, integrated over energy, per incident electron (photon yield). Results were reported at 10-30 MV on the beam axis for Al and Pb targets and at 15 MV at angles out to 90 degrees for Be, Al, and Pb targets. Beam energy was revised with improved accuracy of 0.5% using an improved energy calibration of the accelerator. Recently released versions of the Monte Carlo systems EGSNRC, GEANT4, and PENELOPE were benchmarked against the published measurements using the revised beam energies. Monte Carlo simulation was capable of calculation of photon yield in the experimental geometry to 5% out to 30 degrees, 10% at wider angles, and photon spectra to 10% at intermediate photon energies, 15% at lower energies. Accuracy of measured photon yield from 0 to 30 degrees was 5%, 1 s.d., increasing to 7% for the larger angles. EGSNRC and PENELOPE results were within 2 s.d. of the measured photon yield at all beam energies and angles, GEANT4 within 3 s.d. Photon yield at nonzero angles for angles covering conventional field sizes used in radiotherapy (out to 10 degrees), measured with an accuracy of 3%, was calculated within 1 s.d. of measurement for EGSNRC, 2 s.d. for PENELOPE and GEANT4. Calculated spectra closely matched measurement at photon energies over 5 MeV. Photon spectra near 5 MeV were underestimated by as much as 10% by all three codes. The photon spectra below 2-3 MeV for the Be and Al targets and small angles were overestimated by up to 15% when using EGSNRC and PENELOPE, 20% with GEANT4. EGSNRC results with the NIST option for the bremsstrahlung cross section were preferred over the alternative cross section available in EGSNRC and over EGS4. GEANT4 results calculated with the "low energy" physics list were more accurate than those calculated with the "standard" physics list.

Focused beam-stop array for the measurement of scatter in megavoltage portal and cone beam CT imaging.

We describe a focused beam-stop array (BSA) for the measurement of object scatter in imaging systems that utilize x-ray beams in the megavoltage (MV) energy range. The BSA consists of 64 doubly truncated tungsten cone elements of 0.5 cm maximum diameter that are arranged in a regular array on an acrylic slab. The BSA is placed in the accessory tray of a medical linear accelerator at a distance of approximately 50 cm from the focal spot. We derive an expression that allows us to estimate the scatter in an image taken without the array present, given image values in a second image with the array in place. The presence of the array reduces fluence incident on the imaged object. This leads to an object-dependent underestimation bias in the scatter measurements. We apply corrections in order to address this issue. We compare estimates of the flat panel detector response to scatter obtained using the BSA to those derived from Monte Carlo simulations. We find that the two estimates agree to within 10% in terms of RMS error for 30 cm x 30 cm water slabs in the thickness range of 10-30 cm. Larger errors in the scatter estimates are encountered for thinner objects, probably owing to extrafocal radiation sources. However, RMS errors in the estimates of primary images are no more than 5% for water slab thicknesses in the range of 1-30 cm. The BSA scatter estimates are also used to correct cone beam tomographic projections. Maximum deviations of central profiles of uniform water phantoms are reduced from 193 to 19 HU after application of corrections for scatter, beam hardening, and lateral truncation that are based on the BSA-derived scatter estimate. The same corrections remove the typical cupping artifact from both phantom and patient images. The BSA proves to be a useful tool for quantifying and removing image scatter, as well as for validating models of MV imaging systems.

Monte Carlo simulation of large electron fields.

Two Monte Carlo systems, EGSnrc and Geant4, the latter with two different 'physics lists,' were used to calculate dose distributions in large electron fields used in radiotherapy. Source and geometry parameters were adjusted to match calculated results to measurement. Both codes were capable of accurately reproducing the measured dose distributions of the six electron beams available on the accelerator. Depth penetration matched the average measured with a diode and parallel-plate chamber to 0.04 cm or better. Calculated depth dose curves agreed to 2% with diode measurements in the build-up region, although for the lower beam energies there was a discrepancy of up to 5% in this region when calculated results are compared to parallel-plate measurements. Dose profiles at the depth of maximum dose matched to 2-3% in the central 25 cm of the field, corresponding to the field size of the largest applicator. A 4% match was obtained outside the central region. The discrepancy observed in the bremsstrahlung tail in published results that used EGS4 is no longer evident. Simulations with the different codes and physics lists used different source energies, incident beam angles, thicknesses of the primary foils, and distance between the primary and secondary foil. The true source and geometry parameters were not known with sufficient accuracy to determine which parameter set, including the energy of the source, was closest to the truth. These results underscore the requirement for experimental benchmarks of depth penetration and electron scatter for beam energies and foils relevant to radiotherapy.

Prototyping a large field size IORT applicator for a mobile linear accelerator.

The treatment of large tumors such as sarcomas with intra-operative radiotherapy using a Mobetron is often complicated because of the limited field size of the primary collimator and the available applicators (max Ø100 mm). To circumvent this limitation a prototype rectangular applicator of 80 x 150 mm(2) was designed and built featuring an additional scattering foil located at the top of the applicator. Because of its proven accuracy in modeling linear accelerator components the design was based on the EGSnrc Monte Carlo simulation code BEAMnrc. First, the Mobetron treatment head was simulated both without an applicator and with a standard 100 mm applicator. Next, this model was used to design an applicator foil consisting of a rectangular Al base plate covering the whole beam and a pyramid of four stacked cylindrical slabs of different diameters centered on top of it. This foil was mounted on top of a plain rectangular Al tube. A prototype was built and tested with diode dosimetry in a water tank. Here, the prototype showed clinically acceptable 80 x 150 mm(2) dose distributions for 4 MeV, 6 MeV and 9 MeV, obviating the use of complicated multiple irradiations with abutting field techniques. In addition, the measurements agreed well with the MC simulations, typically within 2%/1 mm.

Helium CT: Monte Carlo simulation results for an ideal source and detector with comparison to proton CT.

PURPOSE: To evaluate the accuracy of relative stopping power and spatial resolution of images reconstructed with simulated helium CT (HeCT) in comparison to proton CT (pCT). METHODS: A Monte Carlo (MC) study with the TOPAS tool was performed to compare the accuracy of relative stopping power (RSP) reconstruction and spatial resolution of low-fluence HeCT to pCT, both using 200 MeV/u particles. An ideal setup consisting of a flat beam source and a totally absorbing energy-range detector was implemented to estimate the theoretically best achievable RSP accuracy for the calibration and reconstruction methods currently used for pCT. The phantoms imaged included a cylindrical water phantom with inserts of different materials, sizes, and positions, a Catphan phantom with a module containing high-contrast line pairs (CTP528) and a module with cylindrical inserts of different RSP (CTP404), as well as a voxelized 10-year-old female phantom. Dose to the cylindrical water phantom was also calculated. The RSP accuracy was studied for all phantoms except the CTP528 module. The latter was used for the estimation of the spatial resolution, evaluated as the modulation transfer function (MTF) at 10%. RESULTS: An overall error under 0.5% was achieved for HeCT for the water phantoms with the different inserts, in all cases better than that for pCT, in some cases by a factor 3. The inserts in the CTP404 module were reconstructed with an average RSP accuracy of 0.3% for HeCT and 0.2% for pCT. Anatomic structures (brain, bones, air cavities, etc.) in the digitized head phantom were well recognizable and no artifacts were visible with both HeCT and pCT. The three main tissue materials (soft tissue, brain, and cranium) were well identifiable in the reconstructed RSP-volume distribution with both imaging modalities. Using 360 projection angles, the spatial resolution was 4 lp/cm for HeCT and 3 lp/cm for pCT. Generally, spatial resolution increased with the number of projection angles and was always higher for HeCT than for pCT for the same number of projections. When HeCT and pCT scan were performed to deliver the same dose in the phantom, the resolution for HeCT was higher than pCT. CONCLUSION: MC simulations were used to compare HeCT and pCT image reconstruction. HeCT images had similar or better RSP accuracy and higher spatial resolution compared to pCT. Further investigation of the potential of helium ion imaging is warranted.

Report of the AAPM Task Group No. 105: Issues associated with clinical implementation of Monte Carlo-based photon and electron external beam treatment planning.

The Monte Carlo (MC) method has been shown through many research studies to calculate accurate dose distributions for clinical radiotherapy, particularly in heterogeneous patient tissues where the effects of electron transport cannot be accurately handled with conventional, deterministic dose algorithms. Despite its proven accuracy and the potential for improved dose distributions to influence treatment outcomes, the long calculation times previously associated with MC simulation rendered this method impractical for routine clinical treatment planning. However, the development of faster codes optimized for radiotherapy calculations and improvements in computer processor technology have substantially reduced calculation times to, in some instances, within minutes on a single processor. These advances have motivated several major treatment planning system vendors to embark upon the path of MC techniques. Several commercial vendors have already released or are currently in the process of releasing MC algorithms for photon and/or electron beam treatment planning. Consequently, the accessibility and use of MC treatment planning algorithms may well become widespread in the radiotherapy community. With MC simulation, dose is computed stochastically using first principles; this method is therefore quite different from conventional dose algorithms. Issues such as statistical uncertainties, the use of variance reduction techniques, the ability to account for geometric details in the accelerator treatment head simulation, and other features, are all unique components of a MC treatment planning algorithm. Successful implementation by the clinical physicist of such a system will require an understanding of the basic principles of MC techniques. The purpose of this report, while providing education and review on the use of MC simulation in radiotherapy planning, is to set out, for both users and developers, the salient issues associated with clinical implementation and experimental verification of MC dose algorithms. As the MC method is an emerging technology, this report is not meant to be prescriptive. Rather, it is intended as a preliminary report to review the tenets of the MC method and to provide the framework upon which to build a comprehensive program for commissioning and routine quality assurance of MC-based treatment planning systems.

Response of intracerebral human glioblastoma xenografts to multifraction radiation exposures.

PURPOSE: We investigated the effects of fractionated radiation treatments on the life spans of athymic rats bearing intracerebral brain tumors. METHODS AND MATERIALS: U-251 MG or U-87 MG human glioblastoma cells were implanted into the brains of athymic rats, and the resulting tumors were irradiated once daily with various doses of ionizing radiation for 5 consecutive days or for 10 days with a 2-day break after Day 5. RESULTS: Five daily doses of 1 and 1.5 Gy, and 10 doses of 0.75 and 1 Gy, cured some U-251 MG tumors. However, five daily doses of 0.5 Gy increased the survival time of animals bearing U-251 MG tumors 5 days without curing any animals of their tumors. Ten doses of 0.3 Gy given over 2 weeks extended the lifespan of the host animals 9 days without curing any animals. For U-87 MG tumors, 5 daily doses of 3 Gy produced an increased lifespan of 8 days without curing any animals, and 10 doses of 1 Gy prolonged lifespan 5.5 days without curing any animals. The differences in extension of life span between the 5- and 10-fraction protocols were minor for either tumor type. CONCLUSION: The finding that the U-251 MG tumors are more sensitive than U-87 MG tumors, despite the fact that U-251 MG tumors contain many more hypoxic cells than U-87 MG tumors, suggests the intrinsic cellular radiosensitivities of these cell lines are more important than hypoxia in determining their in vivo radiosensitivities.

Intraoperative radiation therapy using mobile electron linear accelerators: report of AAPM Radiation Therapy Committee Task Group No. 72.

Intraoperative radiation therapy (IORT) has been customarily performed either in a shielded operating suite located in the operating room (OR) or in a shielded treatment room located within the Department of Radiation Oncology. In both cases, this cancer treatment modality uses stationary linear accelerators. With the development of new technology, mobile linear accelerators have recently become available for IORT. Mobility offers flexibility in treatment location and is leading to a renewed interest in IORT. These mobile accelerator units, which can be transported any day of use to almost any location within a hospital setting, are assembled in a nondedicated environment and used to deliver IORT. Numerous aspects of the design of these new units differ from that of conventional linear accelerators. The scope of this Task Group (TG-72) will focus on items that particularly apply to mobile IORT electron systems. More specifically, the charges to this Task Group are to (i) identify the key differences between stationary and mobile electron linear accelerators used for IORT, (ii) describe and recommend the implementation of an IORT program within the OR environment, (iii) present and discuss radiation protection issues and consequences of working within a nondedicated radiotherapy environment, (iv) describe and recommend the acceptance and machine commissioning of items that are specific to mobile electron linear accelerators, and (v) design and recommend an efficient quality assurance program for mobile systems.

Experimental depth dose curves of a 67.5 MeV proton beam for benchmarking and validation of Monte Carlo simulation.

PURPOSE: To measure depth dose curves for a 67.5 ± 0.1 MeV proton beam for benchmarking and validation of Monte Carlo simulation. METHODS: Depth dose curves were measured in 2 beam lines. Protons in the raw beam line traversed a Ta scattering foil, 0.1016 or 0.381 mm thick, a secondary emission monitor comprised of thin Al foils, and a thin Kapton exit window. The beam energy and peak width and the composition and density of material traversed by the beam were known with sufficient accuracy to permit benchmark quality measurements. Diodes for charged particle dosimetry from two different manufacturers were used to scan the depth dose curves with 0.003 mm depth reproducibility in a water tank placed 300 mm from the exit window. Depth in water was determined with an uncertainty of 0.15 mm, including the uncertainty in the water equivalent depth of the sensitive volume of the detector. Parallel-plate chambers were used to verify the accuracy of the shape of the Bragg peak and the peak-to-plateau ratio measured with the diodes. The uncertainty in the measured peak-to-plateau ratio was 4%. Depth dose curves were also measured with a diode for a Bragg curve and treatment beam spread out Bragg peak (SOBP) on the beam line used for eye treatment. The measurements were compared to Monte Carlo simulation done with geant4 using topas. RESULTS: The 80% dose at the distal side of the Bragg peak for the thinner foil was at 37.47 ± 0.11 mm (average of measurement with diodes from two different manufacturers), compared to the simulated value of 37.20 mm. The 80% dose for the thicker foil was at 35.08 ± 0.15 mm, compared to the simulated value of 34.90 mm. The measured peak-to-plateau ratio was within one standard deviation experimental uncertainty of the simulated result for the thinnest foil and two standard deviations for the thickest foil. It was necessary to include the collimation in the simulation, which had a more pronounced effect on the peak-to-plateau ratio for the thicker foil. The treatment beam, being unfocussed, had a broader Bragg peak than the raw beam. A 1.3 ± 0.1 MeV FWHM peak width in the energy distribution was used in the simulation to match the Bragg peak width. An additional 1.3-2.24 mm of water in the water column was required over the nominal values to match the measured depth penetration. CONCLUSIONS: The proton Bragg curve measured for the 0.1016 mm thick Ta foil provided the most accurate benchmark, having a low contribution of proton scatter from upstream of the water tank. The accuracy was 0.15% in measured beam energy and 0.3% in measured depth penetration at the Bragg peak. The depth of the distal edge of the Bragg peak in the simulation fell short of measurement, suggesting that the mean ionization potential of water is 2-5 eV higher than the 78 eV used in the stopping power calculation for the simulation. The eye treatment beam line depth dose curves provide validation of Monte Carlo simulation of a Bragg curve and SOBP with 4%/2 mm accuracy.

TH2-Polarized CD4(+) T Cells and Macrophages Limit Efficacy of Radiotherapy.

Radiotherapy and chemotherapy following surgery are mainstays of treatment for breast cancer. Although multiple studies have recently revealed the significance of immune cells as mediators of chemotherapy response in breast cancer, less is known regarding roles for leukocytes as mediating outcomes following radiotherapy. To address this question, we utilized a syngeneic orthotopic murine model of mammary carcinogenesis to investigate if response to radiotherapy could be improved when select immune cells or immune-based pathways in the mammary microenvironment were inhibited. Treatment of mammary tumor-bearing mice with either a neutralizing mAb to colony-stimulating factor-1 (CSF-1) or a small-molecule inhibitor of the CSF-1 receptor kinase (i.e., PLX3397), resulting in efficient macrophage depletion, significantly delayed tumor regrowth following radiotherapy. Delayed tumor growth in this setting was associated with increased presence of CD8(+) T cells and reduced presence of CD4(+) T cells, the main source of the TH2 cytokine IL4 in mammary tumors. Selective depletion of CD4(+) T cells or neutralization of IL4 in combination with radiotherapy phenocopied results following macrophage depletion, whereas depletion of CD8(+) T cells abrogated improved response to radiotherapy following these therapies. Analogously, therapeutic neutralization of IL4 or IL13, or IL4 receptor alpha deficiency, in combination with the chemotherapy paclitaxel, resulted in slowed primary mammary tumor growth by CD8(+) T-cell-dependent mechanisms. These findings indicate that clinical responses to cytotoxic therapy in general can be improved by neutralizing dominant TH2-based programs driving protumorigenic and immune-suppressive pathways in mammary (breast) tumors to improve outcomes.